Unveiling racial disparities in prostate cancer using an integrative genomic and transcriptomic analysis

Abstract

Prostate cancer exhibits significant racial disparities, with African American (AA) individuals showing ∼64% higher incidence and 2.3 times greater mortality rates compared to their Caucasian (CA) counterparts. Understanding the complex interplay of genetic, environmental, lifestyle, socioeconomic, and healthcare access factors is crucial for developing effective interventions to reduce this disproportionate burden.

This study aims to uncover the genetic and transcriptomic differences driving these disparities through a comprehensive analysis using RNA sequencing (RNA-seq) and exome sequencing of prostate cancer tissues from both Black and White patients.

Our transcriptomics analysis revealed enhanced activity in pathways linked to immune response and cellular interactions in AA prostate cancer samples, with notable regulation by histone-associated transcription factors (HIST1H1A, HIST1H1D, and HIST1H1B) suggests potential involvement of histone modification mechanisms. Additionally, pseudogenes and long non-coding RNAs (lncRNAs) among the regulated genes indicate non-coding elements' role in these disparities.

Exome sequencing identified unique variants in AA patient samples within key genes, including TP73 (tumor suppression), XYLB (metabolism), ALDH4A1 (oxidative stress), PTPRB (cellular signaling), and HLA-DRB5 (immune response). These genetic variations likely contribute to disease progression and therapy response disparities.

This study highlights the importance of considering genetic and epigenetic variations in developing tailored therapeutic approaches to improve treatment efficacy and reduce mortality rates across diverse populations.